OBJECTIVE: To establish a high performance liquid chromatography (HPLC) method for the determination of 8-methoxypsoralen (8-MOP) in mouse plasma and apply it to a pharmacokinetic study of 8-MOP. METHODS: 8-MOP was separated on a Waters Symmetry18 column (250 mm × 4.6 mm, 5 μm) and determined by HPLC using isocratic elution, and 5-methoxypsoralen was used as internal standard. The mobile phase consisted of methanol-water (55:45, V/V) at a flow rate of 1.0 mL/min. The excitation and emission wavelength of fluorescence detector were set at 334 nm and 484 nm respectively, and the internal standard method was used for quantitative analysis. In the study, 60 healthy ICR male mice were randomly divided into twelve groups. The mice in control group were administered intragastrically with 1% Tween 80, and the mice in the other eleven groups were administered intragastrically with 8-MOP (40 mg/kg). Plasma concentrations of 8-MOP in the mice at different time points after treatment were determined by HPLC. Pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS: The calibration curve of 8-MOP was linear with a correlation coefficient of 0.999 3 over the concentration range of 0.05 to 10 mg/L, and the limit of detection was 0.015 mg/L. The average recoveries of 8? MOP at three different concentrations (0.10, 0.50, 2.5 mg/L) were from 92.5% to 100.6%. The intra-day precision of 8-MOP was from 3.3% to 8.2%, while the inter-day precision was from 3.4% to 6.7% at three spiked concentration levels. The extraction recoveries of 8-MOP were from 90.9% to 92.0%, and the plasma samples could be stored at -80°C for 15 days at least at three spiked concentration levels. 8-MOP could be detected in mouse plasma 5 min after intragastrical administration to the mice (1.4 mg/L). The concentration of 8-MOP in the mouse plasma reached a maximum 2 h after administration, and 8-MOP could still be detected 24 h after administration (1.1 mg/L). t_1/2 was (39.21±3.65) h, C_max was (2.31±0.02) mg/L, t_max was (2.00±0.00) h, and AUC0-t was (33.34±1.19) (h×mg)/L. CONCLUSION The proposed method is accurate and simple,suitable for pharmacokinetics of 8-MOP in mice.
Animals ; Calibration ; Chromatography, High Pressure Liquid ; Male ; Methoxsalen/pharmacokinetics* ; Mice ; Mice, Inbred ICR ; Photosensitizing Agents/pharmacokinetics* ; Plasma ; Random Allocation

OBJECTIVETo study the pharmacokinetics, distribution and excretion of m-THPC in rat models of liver cancer via orthotropic implantation using Walker-256.

METHODSAfter an intravenous injection of m-THPC with 0.3 mg/kg, the concentrations of m-THPC in biological specimens were determined by a fluorescence method. The data obtained were processed with PK-GRAPH pharmacokinetic procedure.

RESULTSThe disposition of m-THPC in rat models of liver cancer Walker-256 was conformed to a two compartment model with T(1/2)α = 1.18 h, T(1/2)β = 22.57 h at the dose of 0.3 mg/kg.m-THPC was shown to be widely distributed to the various tissues. There was a highest drug accumulation in liver and liver cancer, and lowest in skin and muscle. Ratio of m-THPC concentration in the Walker-256 tumor compared to normal tissue reach the peak 24 h after m-THPC administration.

CONCLUSIONSm-THPC is distributed widely and eliminated at a rapid rate in Walker-256 rats. Twenty four hours after m-THPC administration may be the best time for photodynamic therapy of liver cancer.

Animals ; Liver Neoplasms, Experimental ; metabolism ; Male ; Neoplasm Transplantation ; Organophosphorus Compounds ; pharmacokinetics ; Photosensitizing Agents ; pharmacokinetics ; Rats ; Rats, Wistar ; Tissue Distribution

AIMTo investigate the penetration kinetics of xanthotoxin in human skin and stratum corneum.

METHODSThe penetration experiments were accomplished by the deposit of ethanolic xanthotoxin solution onto human skin and stratum corneum mounted on Franz cells. The diffused xanthotoxin in the receptor solution (1.4% human serum albumin) and the retained amount in the skin and in the stratum corneum after 24 h exposure were quantified by using high performance liquid chromatography.

RESULTSXanthotoxin flux was increased with the concentration deposited onto the human skin, and when the concentration is above 2.5 mg x mL(-1), there is no influence on the xanthotoxin flux. Similar results were obtained from the stratum corneum. And the peak time for the flux in the stratum corneum was preceded about 6 h earlier than that of the whole human skin. The retained xanthotoxin amount after 24 h exposure in the skin and in the stratum corneum increased according to the concentration deposited and has the tendency to saturate. The lag time of ethanolic xanthotoxin solution in the whole human skin is significantly higher than that in the stratum corneum (P < 0.05).

CONCLUSIONThe characteristics of penetration kinetics of xanthotoxin will provide the information for concentration choice of topical formulation and give a reference for ultra violet A (UVA) irradiation time confirmation.

Administration, Cutaneous ; Dose-Response Relationship, Drug ; Epidermis ; metabolism ; Female ; Humans ; In Vitro Techniques ; Methoxsalen ; administration & dosage ; pharmacokinetics ; Middle Aged ; Photosensitizing Agents ; administration & dosage ; pharmacokinetics ; Skin ; metabolism ; Skin Absorption ; Time Factors